Hydroxybenzylidene iminophenyl-benzothiazoles

ABSTRACT

Novel 2(2&#39;-hydroxyaminophenyl)benzothiazoles and the Schiff Bases thereof having the formula: ##SPC1## 
     Wherein X represents hydrogen, SO 3  H, alkyl, aryl, cycloalkyl, or halogen; and wherein R 1  and R 2  represent X, amino or N=CHR 3  and one of the radicals R 1  and R 2  must be amino or N=CHR 3  ; R 3  represents alkyl, aryl, cycloalkyl, arylalkyl or nitrogen heterocyclic radicals having 4 or 5 carbon atoms.

This application is a continuation of application Ser. No. 818,386 filedApr. 22, 1969, and Ser. No. 173,667, filed Aug. 20, 1971, both nowabandoned.

The instant invention is directed to novel amino or amido derivative of2(2-hydroxyphenyl) benzothiazoles. In particular, the instant inventionis directed to novel 2(2'-hydroxyaminophenyl)benzothiazoles and theSchiff Bases thereof, such as the2(2'-hydroxyaldiminophenyl)benzothiazoles.

The novel compounds of the instant invention have the general formula:##SPC2##

Wherein X represents hydrogen, SO₃ H, alkyl, aryl, cycloalkyl, nitrogenheterocyclic or halogen; and wherein R₁ and R₂ represent X, amino orN=CHR₃ and one of the radicals of R₁ and R₂ must be amino or N=CHR₃ ; R₃represents alkyl, aryl, cycloalkyl, arylalkyl, nitrogen heterocyclicradicals having 4 or 5 carbon atoms.

The instant invention is further directed to the preparation offluorescent organic compounds such as thehydroxyaminophenylbenzothiazoles and the corresponding Schiff Baseswhich compounds fluoresce with a red hue. In the past, there have beenfew pure organic compounds which fluoresce with a red hue. Compoundspresently employed which fluoresce red are the europium compounds, whichcompounds are conventionally employed in the colored television tubes.These compounds, however, have been found to be exceedingly expensiveand extensive research has been concerned with finding a suitable andinexpensive substitute therefore.

Therefore, it is an object of the instant invention to provide new andnovel benzothiazole compounds.

Another object of the instant invention is to provide benzothiazolecompounds which are suitable as dyes which fluoresce with a red hue.

Yet another object of the invention is to provide novel chemicalintermediates and products which are compounds which fluoresce in thered range.

A still further object of the instant invention is to provide novelorganic compounds which fluoresce with a red hue which can beeconomically produced and which are suitable as color impregnators oftelevision tubes.

These and other objects of the instant invention will become moreevident from the following more detailed discussion thereof.

The novel compounds of the instant invention may be represented by thegeneral formula: ##SPC3##

Wherein X represents hydrogen, SO₃ H, alkyl, aryl cycloalkyl, orhalogen; and wherein R₁ and R₂ represent X, amino or N=CHR₃ and one ofthe radicals R₁ and R₂ must be amino or N=CHR₃ ; R₃ represents alkyl,aryl, cycloalkyl, arylalkyl or nitrogen heterocyclic radicals having 4or 5 carbon atoms.

Suitable alkyl radicals which may be employed for the substituents X,R₁, R₂ and R₃ include alkyl radicals having from 1 to 30 carbon atomssuch as

    Methyl       Ethyl        Propyl                                              Isopropyl    Butyl        Tertiary Butyl                                      Pentyl       Hexyl        Methyl Hexyl                                        Heptyl       Octyl        Nonyl                                               Decyl        Undecyl      Dodecyl                                             Tridecyl     Tetradecyl   Pentadecyl                                          Hexadecyl    Heptadecyl   Octadecyl                                           Nonadecyl    Eicosyl      Docosyl                                             Tricosyl     Pentacosyl   Triacontyl                                      

and are preferably alkyl radicals having 1 to 6 carbon radicals.

Suitable cycloalkyl radicals which may be employed for X, R₁, R₂ and R₃include but are not limited to:

    Cyclopentyl                 Cyclohexyl                                        Cycloheptyl                 Cyclooctyl                                                       Cyclononyl                                                 

and are preferably cycloalkyl radicals having 5 or 6 membered rings. Thephenyl alkyl substituent is a radical having 7 to 10 carbon atoms.

Suitable halogen radicals for X, R₁ R₂ and r₃ incude

           Chloro         Bromo                                                          Fluoro         Iodo                                                           -

and are preferably chloro and bromo-

Aryl radicals for X, R₁, R₂, and R₃ include phenyl or naphthyl whereasthe phenyl ring can be further substituted with radicals includingalkyl, of 1 to 4 carbon atoms, alkoxy of 1 to 9 carbon atoms, halogen asdefined above carboxy, carboxyalkoxyacyl of 5 to 8 carbon atoms and acylamino derivatives. Preferred aryl radicals of those above are phenyl andalkyl, alkoxy or halogen substituted phenyl radicals.

The hydroxy imino phenyl benzothiazole compounds of the presentinvention may be prepared by forming the hydroxyaminophenylbenzothiazole as a chemical intermediate and by reactingthese intermediates with an aldehyde according to the standard Schiffreaction to form the corresponding Schiff Base. Specifically thehydroxyaminophenylbenzethiazole compounds of the instant invention maybe prepared by condensing o-aminobenzenethiol with a particularsalicylic acid in the presence of phosphorus acid chloride. Such amethod of preparation is disclosed in co-pending application, Ser. No.690,376, now U.S. Pat. No. 3,669,979 issued June 13, 1972. In this typeof reaction, i.e. a phosphazo reaction of said U.S. Patent, theo-aminobenzenethiol is condensed with an appropriate salicylic acid inthe presence of phosphorus trichloride. It is theorized that thearomatic amine first reacts with the phosphorus trichloride to form aphosphazo intermediate which intermediate subsequently reacts with thearomatic carboxylic acid to produce the anilide. This type of phosphazoreaction is generally carried out in the presence of an organic solvent.

In general, the solvent that is employed is selected from aromatichydrocarbon compounds and aromatic amines such as benzene, toluene,ortho, meta and paraxylene, dimethyl aniline and the like. Thehydrocarbon solvents and in particular toluene and the aromatic aminessuch as dimethyl aniline are the preferred solvents for use in thepreparation of the novel intermediate compounds of the instantinvention. It has been found that the above two denoted solvents, resultin a slightly higher yield of the desired amino intermediate compoundsas compared to the other solvents which may be employed. The amount ofsolvent used in the preparation of the instant compounds is in no waycritical and an excess thereof may be employed without interfering withthe reaction or adversely affecting the yield or purity of the reactionproduct. The solvent that is employed in the system is readily removedfrom the reaction system subsequent to the completion of the reaction byconventional solvent removal processes.

The process employed in the preparation of the instanthydroxyaminophenylbenzothiazole intermediate compounds is generallycarried out in two stages or steps. The first step in the reaction, i.e.the reaction of the o-aminobenzenethiol and phosphorus trichloride isexothermic and is generally carried out at a temperature from about 40°to 120°C and preferably at a temperature from about 50°C to about 90°Cwith external cooling. In this step the phosphazo intermediate isprepared by the reaction of phosphorus trichloride with theo-aminobenzenethiol. The second stage of the reaction between thephosphazo intermediate and the salicylic acid derivative is generallycarried out in an elevated temperature from about 90° to about 180°C andpreferably from about 105° to 120°C. The temperature employed is mostpreferably near the boiling point of the solvent so that refluxconditions can be utilized for recovering substantially pure product. Ithas been found that if one carries out both steps at an elevatedtemperature, an inferior product in low yield is produced. The processemployed in connection with the instant invention can be carried outeither by employing a single reaction vessel, initially kept at about40° to 120°C with a subsequent raising of the temperature of reaction toa higher temperature up to 180°C or the process may be conducted in twoseparate reaction vessels. If the process is conducted in two separatereaction vessels, the product of the first reaction conducted at a lowertemperature is completely removed and passed into the second vessel at ahigher temperature in order to conduct the second step or stage of thereaction.

The reactants in the above process are employed in substantiallystoichiometric amounts, although it is also permissible to employ anexcess of either of the reactants without comparing the purity, or yieldof the reaction product.

The amount of phosphorus trichloride catalyst employed in the abovereaction may vary greatly from about 0.5 moles to about 2 moles ofphosphorus trichloride per mole of o-aminobenzenethiol or derivativesthereof. Preferably the phosphorus trichloride catalyst and theo-aminobenzenethiol or derivative are employed in substantially equalmolar amounts. It is of course obvious that the lesser or greateramounts of catalyst can be employed where desired.

It has unexpectedly been found that the substitution in the 2' positionof 2-(phenyl)benzothiazoles with a hydroxy substituent results in amarked enhancement of the fluorescent characteristics of the resultantcompounds as compared with the 3' or 4' positions. It is believed thatthe intenseness of the fluorescence of these compounds as compared tothose without 2'hydroxy substituent is due in part to an intramolecularhydrogen bonding which results in an increased copolanarity andtherefore an enhanced fluorescence. This may be depicted by reference tothe following equation, in which the intramolecular hydrogen bonding isillustrated. ##SPC4##

This effect is further established by a comparison of the absolute valueof fluorescence of the numerous hydroxy substitutions possible on thephenyl ring of the benzothiazole. It has been found that, if onesubstitutes a hydroxy substituent in the 2' position, one obtains abrightness number of 41. However, one substitutes the hydroxysubstituent in either the 3' or 4' positions, one obtains a brightnessnumber of only 6 and 11 respectively which variation in fluorescentvalues clearly indicates the unexpected effect of the compounds of theinstant invention. Furthermore, a visual observation ofhydroxyphenylbenzothiazole compounds indicates that the 2' substitutedcompound, i.e. 2(2'-hydroxyphenyl)benzothiazole fluoresces with anintense green fluorescence, whereas the2(3'-hydroxyphenyl)-benzothiazole and 2(4'-hydroxyphenyl)benzothiazolefluoresces with a weak orange fluorescence and a barely perceptibleorange fluorescence respectively. Surprisingly, in the2(2'-hydroxyphenyl)benzothiazole compounds, the substitution of theamino groups or imido in the 3' or 5' positions results in a shifting ofthe fluorescence into the red area, that is to say, that when the aminogroups are substituted in either the ortho or para positions relative tothe hydroxy radical a compound which fluoresces with an intense redresults.

In addition to the amino substituent in the 3' or 5' positions of thebenzothiazole intermediate compounds of the instant invention, thecorresponding Schiff Bases of these compounds have also been found tohave these unique utilities. The corresponding Schiff Base products oraldimines may be readily prepared by the reaction of the correspondingprimary amine, such as the amino intermediates prepared by the abovemethod, with the desired aldehyde according to the following reactionscheme: ##SPC5##

Process of this type are disclosed in Ann Sup., 3,343 (1864), JACS,43,626 (1921) and is basically the standard Schiff reaction. The aboveSchiff reaction is carried out in the presence of an inert solvent suchas an alcohol, methyl, ethyl hetone, acetone at a temperature betweenabout 50°C and about 200°C, preferably under conditions of reflux at thepressure employed; atmospheric pressure being preferred.

The compounds of the instant invention are all water-insoluble. It isnoted, however, that they can be solubilized by sulfonation as describedin the co-pending application of H. B. Freyermuth, Ser. No. 690,791,filed Dec. 15, 1967 now U.S. Pat. No. 3,491,106, or by any otherappropriate sulfonation process known in the art.

The instant invention will now be explained in more detail by referenceto the following examples.

EXAMPLE I

2(2'-hydroxy-5'-aminophenyl)benzothiazole was prepared according to thefollowing reaction process:

61 g. of 5-aminosalicylic acid was reacted with 50 g. ofo-aminobenzenethiol in 500 ml. toluene. The reaction mixture was stirredand heated so as to dissolve the reactors and subsequently cooled to 60°C 17.5 ml. of phosphorus trichloride was then added and the reactionmixture was heated to reflux for 6 hours. At the end of this time thedesired product precipitated and said product was filtered and airdried.

EXAMPLE II

2(2'-hydroxy-5'-benzlideneiminophenyl)benzothiazole was preparedaccording to the following process:

6 g. 2(2'-hydroxy-5'-aminophenyl)benzothiazole was prepared according tothe method in Example I and was reacted with 3.4 g. benzaldehyde in 70ml. of ethanol. The mixture was refluxed for 30 minutes, drowned in iceand the resultant solid product was filtered.

EXAMPLE III

2(2'-hydroxy-3'-aminophenyl)benzothiazole was prepared by reacting3-aminosalicylic acid with o-aminobenzenethiol according to the processof Example I. At the end of 6 hours the desired product precipitated andsaid product was filtered and air-dried.

EXAMPLE IV

The corresponding Schiff Base of the product of the previous example wasprepared according to the process of Example II by reacting said productwith benzaldehyde in ethanol. The mixture was refluxed for thirtyminutes, drowned in ice and the resultant product was filtered.

The following compounds are prepared under the temperature and pressureconditions of the above disclosure and in accordance with the procedureof the above examples by condensing

a. an aminothiophenol having substituents corresponding to thesubstituents of the product in the benzothiazole moiety of the compound(e.g., such as those designated as Compound I in the above reference,U.S. Pat. No. 3,669,979) with

b. aminosalicylic acid having substituents corresponding to thesubstituents of the product in phenol moiety of the compound to producethe corresponding 2(2-hydroxyaminophenyl) benzothiazole having thegeneral formula: ##SPC6##

and/or reacting compound 1 having the desired substitution of the imidoproduct with an aldehyde (e.g., acetaldehyde, ethylaldehyde,propionaldehyde, naphthaldehyde, xyloylaldehyde, halobenzaldehyde,butyraldehyde, tolualdehyde, dimethylbenzaldehyde,dimethoxybenzaldehyde, propylbenzaldehyde, pyridinecarboxaldehyde,pyrimidinecarboxaldehyde, carboxybenzaldehyde, formylbenzaldehyde,indolecarboxaldehyde) to provide the corresponding Schiff Base havingthe general formula: ##SPC7##

Specific products of this invention include the following: ##SPC8####SPC9## ##SPC10## ##SPC11## ##SPC12## ##SPC13##

What is claimed is:
 1. A red fluorescing 2-(2'-hydroxyphenyl)benzothiazole derivative having the formula: ##SPC14##wherein R₁ or R₂is N=CHR₃ and R₃ is aryl selected from the group of phenyl, naphthyl,and phenyl substituted by alkyl having from 1 to 4 carbon atoms or halo,nitrogen heterocyclic radicals having 4 or 5 carbon atoms in anaromatically, unsaturated, 6-membered ring and aryl C₁₋₃₀ alkyl whereinaryl is as defined above; and X and the other of R₁ and R₂ is hydrogen,halogen, alkyl having 1 to 30 carbon atoms, cycloalkyl having 5 to 9carbon atoms, nitrogen heterocyclic as defined above, aryl as definedabove and SO₃ H.
 2. The compound of claim 1 wherein R₃ is phenylethyl,phenyl, tolyl, xylyl, chlorophenyl, naphthyl, pyridyl, pyrazyl and theother of R₁ and R₂ is hydrogen, phenyl or methyl; and X is alkyl having1 to 8 carbon atoms, halogen, phenyl, tolyl, or hydrogen.
 3. Thecompound of claim 1 designated as2(2'-hydroxy-5'-benzylideneiminophenyl)benzothiazole.
 4. The compound ofclaim 1 designated as2(2'-hydroxy-3'-benzylideneiminophenyl)benzothiazole.
 5. The compound ofclaim 1 designated as2(2'-hydroxy-3'-methylbenzylideneiminophenyl)ethylbenzothiazole.
 6. Thecompound of claim 1 designated as2(2'-hydroxy-5'-naphthylideneiminophenyl)benzothiazole.
 7. The compoundof claim 1 designated as2(2'-hydroxy-5'-methylbenzylideneiminophenyl)benzothiazole.
 8. Thecompound of claim 1 designated as2(2'-hydroxy-5'-methylbenzylidineiminophenyl)ethylbenzothiazole.
 9. Thecompound of claim 1 designated as2(2'-hydroxy-5'-ethyliminophenyl)sulfobenzothiazole.
 10. The compound ofclaim 1 designated as2(2'-hydroxy-3'-benzylidineiminophenyl)phenylbenzothiazole.
 11. A redfluorescing 2-(2'-hydroxyphenyl) benzothiazole derivative having theformula: ##SPC15##wherein R₁ or R₂ is N=CHR₃ and R₃ is aryl selectedfrom the group of phenyl, napthyl, and phenyl substituted by alkylhaving from 1 to 30 carbon atoms, alkoxy having from 1 to 9 carbonatoms, and halo;cycloalkyl having from 5 to 9 carbon atoms; nitrogenheterocyclic radicals having 4 or 5 carbon atoms in the ring; andarylalkyl wherein aryl and alkyl are as defined above; and X and theother of R₁ and R₂ is hydrogen; halogen; alkyl having 1 to 30 carbonatoms; cycloalkyl having 5 to 9 carbon atoms; nitrogen heterocyclic asdefined above; aryl as defined above and SO₃ H.